Anti-cancer strain expressing strep-tag, anti-cancer composition using the same, anti-cancer adjuvant and tumor imaging agent

Abstract

The present invention relates to a gene construct characterized by encoding a fusion protein of flgM and Strep-tag through the linkage of an anti-sigma factor flgM gene and a gene encoding Strep-tag, enabling the expression of Strep-tag on the surface of an anti-cancer strain that can target tumor sites and stimulate immune activity, and to an anti-cancer adjuvant and tumor imaging agent that, when transformed by this construct, exhibits anti-cancer activity itself and can be effectively utilized in the diagnosis and treatment of tumor cells together with anti-cancer substances or contrast agents labeled with substances specifically interacting with Strep-tag.

1 . A gene construct characterized by encoding a fusion protein of flgM and Strep-tag through the linkage of an anti-sigma factor flgM gene and a gene encoding Strep-tag. 
     
     
         2 . The gene construct according to  claim 1 ,
 wherein the flgM gene and gene encoding strep-tag are directly linked or linked via a linker.   
     
     
         3 . The gene construct according to  claim 1 ,
 wherein it consists of SEQ ID NO: 1 or SEQ ID NO: 2.   
     
     
         4 . A recombinant expression vector comprising the gene construct of  claim 1 . 
     
     
         5 . An anti-cancer recombinant strain that is transformed with the gene construct of  claim 1  operably linked to an inducible promoter, wherein the strain is characterized by expressing fusion protein of flgM and Strep-tag on the surface of the strain, secreting fusion protein of flgM and Strep-tag, or both expressing fusion protein of flgM and Strep-tag on the surface of the strain and secreting it, and targeting tumor cells. 
     
     
         6 . The anti-cancer recombinant strain according to  claim 5 , wherein the strain is an attenuated Salmonella strain. 
     
     
         7 . The anti-cancer recombinant strain according to  claim 6 ,
 wherein the strain has inhibited or lost motility when expressing fusion protein of flgM and strep-tag by the inducible promoter.   
     
     
         8 . The anti-cancer recombinant strain according to  claim 7 ,
 wherein the strain is the strain with deposit number KCTC15484BP.   
     
     
         9 . A method of treating a cancer, comprising:
 administering an anti-cancer composition comprising the anti-cancer recombinant strain of  claim 5  to a subject.   
     
     
         10 . An anti-cancer adjuvant characterized by comprising the recombinant strain of  claim 5  and being co-administered with an anti-cancer agent labeled with a substance that specifically binds to Strep-tag. 
     
     
         11 . The anti-cancer adjuvant according to  claim 10 ,
 wherein the substance that specifically binds to Strep-tag is avidin, streptavidin or Strep-tactin.   
     
     
         12 . A tumor imaging adjuvant characterized by comprising the recombinant strain of  claim 5  and being co-administered with a contrast agent labeled with a substance that specifically binds to Strep-tag. 
     
     
         13 . The tumor imaging adjuvant according to  claim 12 ,
 wherein the substance that specifically binds to Strep-tag is avidin, streptavidin or Strep-tactin.   
     
     
         14 . The tumor imaging adjuvant according to  claim 12 ,
 wherein the contrast agent is one or more selected from the group consisting of radioactive nuclides, fluorescent labels, enzyme labels, chemiluminescent markers, gold preparations and magnetic preparations.   
     
     
         15 . A method for providing information for cancer diagnosis comprising:
 (A) targeting tumor cells by administering the tumor imaging adjuvant of claim  14  to a patient suspected of having cancer or undergoing anti-cancer treatment;   (B) inducing expression of flgM and strep-tag fusion protein in the recombinant strain of the tumor imaging adjuvant;   (C) administering a contrast agent labeled with a substance that specifically binds to Strep-tag; and   (D) detecting and imaging the contrast agent.